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Molecular Profiling of Spinal Disease Progression in Ankylosing Spondylitis

Award Number: K23AR083506
ORGANIZATION: NATIONAL INSTITUTE OF ARTHRITIS & MUSCULOSKELETAL & SKIN DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP
PERIOD OF PERFORMANCE START DATE: 02/12/2024
PERIOD OF PERFORMANCE END DATE: 01/31/2029

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Molecular Profiling of Spinal Disease Progression in Ankylosing Spondylitis - PROJECT SUMMARY/ABSTRACT Ankylosing spondylitis (AS) is a chronic inflammatory arthritis with a predilection for the spine and sacroiliac joints, affecting 0.5-0.6% of the US population, that causes substantial morbidity and work-disability. AS spinal damage is strongly related to poor physical function independent of disease activity - severe spinal disease causing significant physical limitations. However, the course of AS spinal disease is highly heterogeneous, ranging from damage limited to sacroiliac joints to complete spinal fusion. We characterized AS patients' longitudinal spinal progression over a 15-year interval, revealing 4 endotypes/groups of spinal progression. However, clinical variables poorly discriminated patients who developed severe spinal disease compared to the other spinal disease groups. Our goals in this proposal are to i) characterize the peripheral blood molecular profile of AS spinal disease and ii) develop prediction tools combining clinical and molecular biomarkers prognosticate AS spinal disease before irreversible damage has occurred. The PI's preliminary data indicate that peripheral blood molecular markers in combination with genetic and clinical variables improve prognostication of long-term spinal outcomes. Aim 1 of the proposal is designed to further profile the transcriptomic signatures associated with AS spinal disease progression through next- generation bulk and single-cell RNA-sequencing. Aim 2 will use high-throughput proteomics to profile AS patients' sera with known AS spinal trajectories. Aim 3 will use Bayesian multivariable modeling and Integrative analysis of clinical, genetic, gene expression and proteomic datasets to generate prediction models of AS patients' risk of severe spinal disease. The Pl is an MD Rheumatologist with the long-term goal of becoming an independent investigator focused on AS pathogenesis and outcomes. The proposed research and training plan will help the Pl to develop proficiency in analyses of molecular data and in systems medicine modeling. Equally important are the career development goals of enhancing skills in data presentation, grant writing and project management in preparation for scientific independence. These goals will be achieved through a combination of mentorship, formal didactic instruction, and experimentation. The work will be performed in an excellent institutional environment with mentorship from Dr.Shervin Assassi, a leader in molecular profiling in systemic sclerosis, and additional guidance from co-mentors with expertise in ankylosing spondylitis, bioinformatics and immunology. This award will accelerate the Pl's research as well as career development into an independent and productive clinician scientist in rigorously designed and conducted translational research.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $162,540 )
2026	2026	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT HOUSTON	7000 FANNIN ST FL 9	HOUSTON	TX	77030	HARRIS	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	3	1/30/2026	NON-COMPETING CONTINUATION	$162,540
														Subtotal = $162,540

Issue Date FY: 2025 ( Subtotal = $162,540 )
2025	2025	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT HOUSTON	7000 FANNIN ST FL 9	HOUSTON	TX	77030	HARRIS	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	2	2/14/2025	NON-COMPETING CONTINUATION	$162,540
														Subtotal = $162,540

Issue Date FY: 2024 ( Subtotal = $162,540 )
2024	2024	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT HOUSTON	7000 FANNIN ST FL 9	HOUSTON	TX	77030	HARRIS	USA	Arthritis, Musculoskeletal and Skin Diseases Research	001	1	2/13/2024	NEW	-$162,540
2024	2024	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT HOUSTON	7000 FANNIN ST FL 9	HOUSTON	TX	77030	HARRIS	USA	Arthritis, Musculoskeletal and Skin Diseases Research	002	1	2/16/2024	NEW	$162,540
2024	2024	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT HOUSTON	7000 FANNIN ST FL 9	HOUSTON	TX	77030	HARRIS	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	1	2/12/2024	NEW	$162,540
														Subtotal = $162,540

Grand Total All Awards = $487,620

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Molecular Profiling of Spinal Disease Progression in Ankylosing Spondylitis

Award Number: K23AR083506

ORGANIZATION: NATIONAL INSTITUTE OF ARTHRITIS & MUSCULOSKELETAL & SKIN DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

PERIOD OF PERFORMANCE START DATE: 02/12/2024

PERIOD OF PERFORMANCE END DATE: 01/31/2029

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